Consultation with the Specialist: The Long QT Syndrome
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PIR-july98DOI: 10.1542/pir.19-7-232 1998;19;232Pediatrics in
Review
Michael J. Ackerman Consultation with the Specialist: The Long QT
Syndrome
http://pedsinreview.aappublications.org/content/19/7/232 World Wide
Web at:
The online version of this article, along with updated information
and services, is located on the
© 1998 by the American Academy of Pediatrics. All rights reserved.
Print ISSN: 0191-9601. American Academy of Pediatrics, 141
Northwest Point Boulevard, Elk Grove Village, Illinois, 60007.
Copyright been published continuously since 1979. Pediatrics in
Review is owned, published, and trademarked by the Pediatrics in
Review is the official journal of the American Academy of
Pediatrics. A monthly publication, it has
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JA, a 3-month-old boy, was diagnosed with gastroesophageal reflux
disease and treated with ranitidine (a histamine-2- blocker) and
cisapride (a promotility agent). He was brought to the emergency
department after his mother found him cyanotic and unresponsive in
his crib. Cardiac monitoring documented ventric- ular tachycardia.
Cardioversion was successful, and follow-up ECG demon- strated a
prolonged QT interval. Addi- tionally, the serum level of cisapride
was elevated.
JK is a previously healthy 10-year- old boy who was retrieved from
the bottom of a public swimming pool and defibrillated at poolside
from a torsade de pointes ventricular arrhythmia. He was racing his
younger brother at the time of the near-drowning. ECGs obtained
from the boy and available family members confirmed the diagnosis
of congenital long QT syndrome in the boy and several others.
LA is a 15-year-old boy who has marked seasonal allergic rhinitis
that has been well controlled for 3 years with astemizole (a
nonsedating antihistamine). This fall he presented to his
pediatrician after having multiple syncopal events over a 2-week
period. After careful inquiry, the physician discovered that the
boy had been taking ketoconazole for a short time for a presumed
fungal infection. Suspecting acquired long
QT syndrome, the pediatrician obtained an ECG, which demonstrated a
pro- longed corrected QT interval (QTc ~0.5 sec1/2). The patient
has remained free of syncope since discontinuing the ketoconazole.
Further, management of his allergic rhinitis was changed to a
“heart-friendly” antihistamine (eg, loratidine).
MK is a 2-year-old girl who is being evaluated for speech delay.
She is the youngest of three living siblings. Another child died at
4 months of age from sud- den infant death syndrome (SIDS). Hearing
evaluation confirms the parent’s suspicion that the child is deaf.
ECGs identified the presence of Jervell and Lange-Nielsen syndrome.
Both this child and her parents had prolonged QT intervals.
LD is a 6-week-old infant who was admitted to the hospital
following parox- ysmal coughing spells. Pertussis infec- tion was
established by nasopharyngeal culture, and the infant was started
on a 14-day course of erythromycin. Ten days into the antibiotic
therapy, a code 45 was called after her monitor indicated a ven-
tricular arrhythmia and apnea. She was revived. A review of her
medications showed that her reflux medication (cis- apride) had not
been discontinued when antibiotic therapy was initiated. An ECG
confirmed the prolonged QT interval.
TA is a 17-year-old competitive athlete who collapsed suddenly
during overtime of the state basketball cham- pionships.
Hypertrophic cardiomyopathy was suspected, but an echocardiogram
revealed no abnormalities. An ECG demonstrated a corrected QT
interval of 0.44 sec1/2 (borderline). However, closer inspection of
the ECG revealed bizarre, notched T waves. The young man reported
taking no medications, the drug screen was negative, and there were
no electrolyte abnormalities. After the young man was stabilized,
careful ques- tioning revealed that this was not his first spell;
he had had several previous syncopal episodes. He recalled passing
out once when a teammate had “scared” him in the locker room. The
initial nega- tive family history was later amended to
include a paternal uncle who had died at age 30 in an unexplained
single-vehicle automobile accident. ECGs revealed clearly prolonged
QT intervals in the patient’s father and in one of the deceased
uncle’s children.
Introduction These cases illustrate the myriad ways that the long
QT syndrome (LQTS) conceals itself, lying in wait for the
opportunity to transform the once peaceful, periodic lub-dub of the
heart into a chaotic heap of asynchrony. Detective-like inquiry is
required to unveil LQTS in individ- uals and families. LQTS crosses
all pediatric disciplines, requiring the pediatrician to understand
the syn- drome, what triggers it, how and in whom this diagnosis
should be sought and verified, and what can be done for those who
harbor this ticking time bomb.
Definition LQTS is so named because of its trademark feature on ECG
(Fig. 1A) in which the QT interval measured from the start of the
QRS complex to the end of the T wave is pro- longed. In addition,
the morphology of the T waves often is peculiar. With appropriate
stimuli, the orderly periodicity of the heart degenerates into a
polymorphic ventricular tachycardia known as torsade de pointes
(“twisting of the points”), the hallmark arrhythmia heralded by
LQTS. Individuals who have LQTS are susceptible to syncope,
seizures, and sudden cardiac death.
Over the past 5 years, scientific breakthroughs have revealed the
molecular basis for LQTS (Fig. 1B). Ion channels, fundamental mem-
brane proteins that govern the elec- trical activity in the heart,
are defec-
232 Pediatrics in Review Vol. 19 No. 7 July 1998
*Department of Pediatrics and Adolescent Medicine, Mayo Eugenio
Litta Children’s Hospital, Mayo Foundation, Rochester, MN.
Consultation with
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Pediatrics in Review Vol. 19 No. 7 July 1998 233
FIGURE 1. Molecular breakthroughs in LQTS. A. The hallmark clinical
features of LQTS. Common presentations include syncope, seizures,
and sudden death resulting from a ventricular arrhythmia, often of
the torsade de pointes variety, stemming from an abnormally
prolonged QT interval. B. The four ion channelopathies, including
their linear topologies and identified mutations, that have been
established as the molecular basis of LQTS. The designation of
channel mutants is such that X###Y means that amino acid X has been
replaced by amino acid Y at position ###. Mutations denoted in a
red-violet rectangle represent ones that have been characterized
functionally. Orange-highlighted mutations found in LQT1 and LQT5
represent the Jervell and Lange-Nielsen syndrome mutations.
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Etiology Once considered an exceedingly rare condition, LQTS more
correctly should be viewed as an unrecog- nized one. The diagnosis
often remains concealed because the sub- stantial variety of drugs,
electrolyte abnormalities, and underlying med- ical conditions that
can give rise to the acquired (iatrogenic) forms of LQTS are not
disclosed (Table 1). Numerous drugs can cause QT interval
prolongation and torsade de pointes. Antiarrhythmics, especially
quinidine, are implicated most com- monly in acquired LQTS, but
other drugs have the potential to cause the syndrome, including
certain antibiotics such as erythromycin, pentamidine, and
trimethoprim- sulfamethoxazole; antifungal agents such as
fluconazole, itraconazole, and ketoconazole; and promotility drugs
such as cisapride. Concomi- tant use of the agents appears to carry
particularly significant risk. Antidepressants such as amitripty-
line can elicit cardiac arrhythmias. Patients who have eating
disorders are at particular risk of LQTS and ventricular
arrhythmias because of the combination of prolonged QT interval and
severe bradycardia in many who suffer from anorexia nervosa.
Electrolyte derangements (low “lytes” cause long QT) also can yield
the acquired LQTS. Syncope, seizures, or cardiac events that occur
in the setting of brisk diuresis (acute hypokalemia); in head
trauma that is associated with aggressive hyper- ventilation (acute
hypokalemia); and in transplantation in which the immunosuppression
regimen includes cyclosporin (chronic hypo- magnesemia) should
prompt the consideration of acquired LQTS and assessment of
electrolyte status.
The congenital forms of LQTS often masquerade as epilepsy or
vasovagal events or remain com- pletely concealed. Key family
facts, such as unexplained fatal accidents,
SIDS, and familial epilepsy or familial fainting spells, either are
not sought or, if elicited, are not considered pertinent in the
evalua- tion of a child having syncope. The Jervell and
Lange-Nielsen syndrome is very rare, occurring in 1 to 6 per 1
million individuals and inherited in an autosomal recessive manner.
Four decades after the original clini- cal description of a
Norwegian fam- ily in whom four of six children had prolonged QT
interval, congenital sensorineural hearing loss, and recurrent
syncope and three of the children died suddenly, the molecu- lar
basis (mutations in a cardiac potassium channel, KVLQT1, and its
beta-subunit, minK) is now known (Fig. 1B, Table 2).
The other inherited form of LQTS, autosomal dominant in Romano-Ward
syndrome, is not rare. Rather, it is vastly under- diagnosed. This
syndrome initially was described in the early 1960s
after noting families who exhibited QT prolongation, syncope, and
sud- den death. Today, Romano-Ward syndrome is viewed as a hetero-
geneous collection of at least six distinct molecular genotypes,
with LQT1-3, 5 resulting from defective cardiac ion channels, LQT4
linked to chromosome 4q25-27 (no candi- date gene has been
identified), and LQT6 reserved for future assign- ments because
several families remain unlinked.
Romano-Ward syndrome is estimated to occur in at least 1 in 10,000
individuals (up to 50,000 persons in the United States). There is
no gender or ancestral preference. Furthermore, inherited LQTS is
believed to account for 4,000 sudden deaths in children and young
adults annually. To place this incidence in context, the
Romano-Ward syn- drome may occur three times as often as the most
common child- hood malignancy, acute lympho-
234 Pediatrics in Review Vol. 19 No. 7 July 1998
TABLE 1. Acquired Causes of Long QT Syndrome
Drugs • Antianginals • Antiarrhythmics
mide, sotalol • Antibiotics (erythromycin, pentamidine,
trimethoprim-sulfamethoxazole) • Antidepressants (tricyclics such
as amitriptyline and desipramine) • Antifungals (fluconazole,
itraconazole, ketoconazole) • Antihistamines (astemizole,
terfenadine [removed from the market for
this reason]) • Antipsychotics (haloperidol, respiridone,
phenothiazines such as
thioridazine) • Lipid-lowering agents (probucol) • Oral
hypoglycemics (glibenclamide, glyburide) • Organophosphate
insecticides • Promotility agents (cisapride)
Electrolyte Disturbances • Acute hypokalemia (associated with
diuretics and hyperventilation) • Chronic hypocalcemia • Chronic
hypokalemia • Chronic hypomagnesemia
Underlying Medical Conditions • Arrhythmias (complete AV block,
severe bradycardia, sick sinus
syndrome) • Cardiac (anthracycline cardiotoxicity, congestive heart
failure, myo-
carditis, tumors) • Endocrine (hyperparathyroidism, hypothyroidism,
pheochromocytoma) • Neurologic (encephalitis, head trauma, stroke,
subarachnoid hemorrhage) • Nutritional (alcoholism, anorexia
nervosa, liquid protein diet, starvation)
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blastic leukemia; one third as often as cystic fibrosis, the most
common ultimately fatal genetic condition in Caucasians; and twice
as often as phenylketonuria, a common disease revealed in routine
newborn screen- ing in Caucasians.
Presentation The inherited LQTS can strike swiftly. One third of
previously “healthy” children and young adults killed suddenly by
LQTS may have sudden death as their first and last symptom. In
general, approximately
60% of patients present with activ- ity- or emotion-related
symptoms— primarily syncope, seizures, and palpitations (Fig. 2).
If these symp- toms are related to the “fight, flight, or fright”
response, LQTS should be considered strongly. Syncope, which
accounts for one third of LQTS presentations, occurs in the setting
of intense adrenergic arousal 60% of the time, with intense emo-
tion and rigorous exercise implicated in more than 50% of cases.
Interest- ingly, swimming appears to be a particular trigger (15%),
as are abrupt auditory signals (8%), such as the doorbell, alarm
clock, tele- phone, or smoke detector.
Inherited LQTS often is misdiag- nosed as epilepsy because it
presents with a generalized seizure in 10% of cases. It is not
known how fre- quently a diagnosis of a primary generalized seizure
disorder actually is LQTS (see the first case study). A careful
history may reveal LQTS as the etiology of “epilepsy.” In LQTS, the
seizures are due to the cerebral ischemia that results from the
ventricular arrhythmia. There- fore, LQTS should be considered
strongly in an adolescent or young
Pediatrics in Review Vol. 19 No. 7 July 1998 235
TABLE 2. Congenital Causes of Long QT Syndrome
Autosomal Dominant (Romano-Ward Syndrome) • Isolated susceptibility
to ventricular arrhythmias, normal hearing
– LQT1 (30% to 50%)—chromosome 11p15.5—KVLQT1—potassium channel
(IKs)
– LQT2 (20% to 30%)—chromosome 7q35-36—HERG—potassium channel
(IKr)
– LQT3 (5% to 10%)—chromosome 3p21-24—SCN5A—sodium channel
(INa)
– LQT4 (?%)—chromosome 4q25-27—gene? – LQT5 (?%)—chromosome
21q22.1-22.2—KCNE1—beta-subunit
(minK) of potassium channel (IKr and IKs) – LQT6
(?%)—chromosome?
Autosomal Recessive (Jervell and Lange-Nielsen Syndrome) •
Associated with sensorineural hearing loss
– JLN1—chromosome 11p15.5—KVLQT1 – JLN2—chromosome
21q22.1-22.2—KCNE1 (minK)
LQTS With Syndactyly • Inheritance?, gene?
Sporadic (?)
FIGURE 2. Clinical presentation of the LQTS. Family history is very
common, as is the presence of symptoms, often adrenergic-
precipitated episodes. Importantly, 40% of individuals who have
LQTS are asymptomatic and are identified only after screening of
family members of a symptomatic index case.
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adult who describes the following sequence: dizziness, lightheaded-
ness, blackouts, loss of conscious- ness, and then seizure. In
young children who cannot provide such a chronology, a history of
loss of consciousness preceding a seizure may suggest LQTS.
Importantly, more than one third of patients who have LQTS are
asymptomatic. Most (75%) of these individuals are identified during
rou- tine screening of family members.
Evaluation Figure 3 illustrates individuals in whom LQTS should be
suspected and the evaluation they should receive. A 12-lead ECG is
the cur- rent screening tool for identification of LQTS. If an ECG
is obtained for this purpose, the physician must carefully inspect
and determine the corrected QT interval (QTc), verify-
ing the computer read-out. The QTc is derived by dividing the
measured QT interval by the square root of the preceding R-R
interval (Bazett’s for- mula used to “correct” the QT inter- val
for heart rate). However, it is impractical to recall this formula,
and few readily know how to calcu- late the QTc based upon
it.
Figure 3 provides a simple nomo- gram that enables the physician to
measure the QT interval and pre- ceding R-R interval in millimeters
with a ruler/caliper and plot it on the chart. The QTc lines of
0.42 sec1/2
and 0.46 sec1/2 have been drawn. A plot falling on or above the top
(solid, 0.46 sec1/2) line is abnormal and represents LQTS with a
posi- tive and negative predictive value exceeding 90%. A plot
landing in the borderline zone indicates a QTc between 0.42 sec1/2
and 0.46 sec1/2
and requires careful decision-mak- ing. At least 5% of known
LQTS
carriers (by genetic mutation) ex- hibit such a QTc. A borderline
QTc in the setting of compatible symptoms or strong family history
is consistent with LQTS. Figure 3 also highlights some of the
peculiar T wave morphologies noted in LQTS. If such abnormalities
are recognized on the ECG, the diag- nosis of LQTS still is
possible even with a borderline QTc. Finally, a plot falling below
the bottom (dashed, 0.42 sec1/2) line is not likely to be LQTS
(~99% negative predictive value). Examining whether the measured QT
interval is greater than 50% of the R-R interval has been suggested
as a quick screen for LQTS, but this approach should be abandoned
in preference to application of this QTc nomogram because it can
result in a high rate of misclassification.
With this understanding of inter- preting the ECG, determining
the
236 Pediatrics in Review Vol. 19 No. 7 July 1998
FIGURE 3. Evaluation of suspected long QT syndrome. The panel on
the left lists scenarios in which a 12-lead ECG is indi- cated. The
center panel provides an easily used QTc nomogram to confirm the
accuracy of the computer-generated QTc and identify affected
individuals. Using an ECG displayed at standard speed (25 mm/sec),
the physician can plot the ruler intersec- tion of the QT interval
and RR interval measured in millimeters. Determinations falling on
or above the QTc = 0.46 sec1/2 line likely identify a patient who
has LQTS and should be referred to a pediatric cardiologist. A
patient who has compatible symp- toms and a borderline ECG (plot
falling between a QTc of 0.42 sec1/2 and 0.46 sec1/2) also should
be referred. The panel on the right illustrates some T-wave
abnormalities that can be seen in LQTS.
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QTc, and inspecting the T waves, in whom should a physician suspect
LQTS and thus obtain an ECG? Importantly, all patients who have
syncope precipitated by emotions, exercise, or exertion and all
first- degree relatives of a patient in whom LQTS is suspected must
have an ECG. Any child who has a prolonged QTc (≥0.46 sec1/2) or a
compelling borderline QTc (symptoms, family history, unusual T
waves) should be referred to a pediatric cardiologist for further
evaluation and treatment. Further evaluation may include a 24-hour
ambulatory electrocardiographic monitor, a stress/exercise ECG, or
repetition of the ECG in the sitting/standing position in an effort
to bring out subtle abnor- malities in ventricular repolarization.
The cardiologist should coordinate screening of the identified
patient’s family, initiate appropriate therapy, and refer the
family for genetic counseling.
Treatment The 10-year mortality rate of untreated LQTS may exceed
50%; with therapy, this rate decreases to approximately 5%.
Standard management options include beta- blocker therapy,
implantation of a pacemaker and/or defibrillator, and a surgical
procedure that involves a left cervicothoracic sympathetic
ganglionectomy. All symptomatic patients should be treated with one
or a combination of these therapies. The role of the primary
physician is to monitor compliance, watch for troublesome side
effects such as depression/mood changes and bronchospasm, and
facilitate treatment adjustments in the face of breakthrough
symptoms. In most cases, the presence of asthma has not precluded
the successful use of beta-blocker therapy. It is vital to remind
these patients to avoid medications known to trigger cardiac
arrhythmias (Table 1). Finally, the physician often serves as the
contact point when a previ- ously asymptomatic but suspected LQTS
family member becomes symptomatic. It is paramount to institute
appropriate therapy promptly.
Unfortunately, the opportunity for such a lifesaving intervention
is not always available, which has led some experts to suggest that
every individual who has inherited LQTS, whether or not
symptomatic, be treated. Proponents of this approach cite that
nearly one third of individ- uals who die suddenly from LQTS have
sudden death as their present- ing symptom. In a large follow-up
study of LQTS in children, two thirds of those experiencing sudden
death were asymptomatic for more than 1 year prior to their death.
Certainly, asymptomatic individuals whose presenting QTc exceeds
0.6 sec1/2 should be treated because this degree of QT prolongation
is a particularly poor prognostic factor. On the other hand, it may
be diffi- cult to justify treating the asympto- matic 50-year-old
who just has been identified as part of a family screen- ing. He or
she already may have passed the test of time and is likely to have
a “friendly” phenotype. Risks and benefits of treating asymptomatic
family members must be weighed carefully by the primary physician,
the cardiologist, and the family.
It also is important for the pri- mary care provider to reinforce
the no competitive sports policy because intense physical exertion
can be deadly. Once properly treated, indi- viduals who have LQTS
can par- ticipate in recreational sports, but moderation and the
presence of a “buddy” are key. Parents, teachers, and “buddies”
must be made aware that a fainting episode or onset of seizure-like
activity in a child who has LQTS requires immediate atten- tion. If
the episode persists for more than a few seconds, prompt activa-
tion of the 911 system is paramount because cardiopulmonary
resuscita- tion and early defibrillation may be critical to saving
the child’s life. Because swimming is known as an arrhythmogenic
trigger, affected individuals never should enter the water
alone.
For acquired LQTS, intravenous magnesium is used to stabilize the
heart’s rhythm while offending drugs, electrolyte abnormalities,
and underlying medical conditions known to precipitate torsade de
pointes are sought and ameliorated.
Future Research The decade of the 1990s has ushered in the
molecular era for LQTS. Revelations that defects in funda- mental
cardiac ion channel proteins are responsible for this syndrome have
created a molecular model of arrhythmogenesis. This model offers
exciting prospects to address the menace of unexpected cardiac
deaths due to ventricular arrhyth- mias, which account for some
300,000 deaths in the United States each year.
Hopefully, the next millennium will bring forth genotype-phenotype
correlations as the natural clinical history of specific ion
channel muta- tions is delineated. These discoveries will allow
better patient counseling about particular risk factors for a
sudden cardiac death and address the important question of which
asymptomatic patients require treat- ment. For example, swimming
may be found not to be a worrisome trigger in individuals who have
mutation X.
In addition, LQTS will become a molecular diagnosis rather than a
clinical, ECG-based diagnosis, which will permit presymptomatic
diagnosis and early, appropriate intervention. Finally, the future
holds great promise for genotype- targeted therapies. Individuals
who have potassium channel mutants (LQT1, LQT2, and LQT5) may
benefit from potassium channel openers; those who have defective
cardiac sodium channels (LQT3) may do well with sodium channel
blockers such as mexiletine.
Summary The LQTS is no longer the rare “zebra” whose purpose is to
ensure that trainees recall that deafness and sudden cardiac death
may be related (Jervell and Lange-Nielsen syndrome). Over the past
10 to 20 years, the number of cases of inherited LQTS (Romano-Ward
syndrome) has increased dramati- cally. It is doubtful that this
reflects a true increase in incidence of dis- ease due to a greater
rate of sporadic gene mutations occurring in the heart or because
of a rising inci- dence of consanguinity. Rather, the “incidence”
of LQTS has risen
Pediatrics in Review Vol. 19 No. 7 July 1998 237
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SUGGESTED READING Ackerman MJ. The long QT syndrome: ion
channel diseases of the heart. Mayo Clin Proc.
1998;73:250–269
Ackerman MJ, Clapham DE. Ion channels: basic science and clinical
disease. N Engl J Med. 1997;336:1575–1586
Ackerman MJ, Porter CJ. Identification of a family with inherited
long QT syndrome following a pediatric near drowning. Pediatrics.
1998;101:306–308
Garson AJ, Dick M, Fournier A, et al. The long QT syndrome in
children. An interna- tional study of 287 patients. Circulation.
1993;87:1866–1872
Keating MT. The long QT syndrome. A review of recent molecular
genetic and physiologic discoveries. Medicine. 1996; 75:1–5
Schwartz PJ, Moss AJ, Vincent GM, Cramp- ton RS. Diagnostic
criteria for the long QT syndrome: an update. Circulation. 1993;
88:782–784
238 Pediatrics in Review Vol. 19 No. 7 July 1998
PIR QUIZ 7. In addition to a prolonged QT inter-
val, an individual who has Jervell and Lange-Neilsen syndrome is
most likely to have: A. Alopecia universalis. B. Cranial bruits. C.
Hepatosplenomegaly. D. Rotary nystagmus. E. Sensorineural hearing
loss.
8. The sport you are most likely to suggest that patients who have
LQTS avoid is: A. Bicycling. B. Bowling. C. Ice skating. D.
Swimming. E. Tennis.
9. The cut-off at which an individual has a 1% or less chance of
having the LQTS is a corrected QT interval of less than: A. 0.42
sec1/2. B. 0.43 sec1/2. C. 0.44 sec1/2. D. 0.45 sec1/2. E. 0.46
sec1/2.
10. A 16-year-old athlete has a synco- pal episode immediately
following a high school basketball game. Evaluation reveals a QTc
of 0.52 sec1/2. Which of the follow- ing family members would you
recommend must have a screening electrocardiogram? A. All
first-degree relatives. B. Brothers and male first cousins. C.
Sisters and female cousins. D. Father and both grandfathers. E.
Mother and both grandmothers.
History of Macrolide Use in Pediatrics. Klein JO. Pediatr Infect
Dis J. 1997;16: 427–431
Cost and Wastage of Antibiotic Suspen- sions: A Comparative Study
for Various Weight Groups. Detar E, Mori G, Beaman D, Kumar A.
Pediatr Infect Dis J. 1997; 16:619–622
A Prospective Study of the Impact of Com- munity-based Azithromycin
Treatment of Trachoma on Carriage and Resistance of Streptococcus
pneumoniae. Leach AJ, Shelby-James TM, Mayo M, et al. Clin Infect
Dis. 1997;24:356–362
The Effect of Changes in the Consumption of Macrolide Antibiotics
on Erythro- mycin Resistance in Group A Strepto- cocci in Finland.
Seppälä H, Klaukka T, Vuopio-Varkila J, et al. N Engl J Med.
1997;337:441–446
Principles of Judicious Use of Antimicro- bial Agents for Pediatric
Upper Respira- tory Tract Infections. Dowell SF, ed. Pediatrics.
1998;101(suppl):163–184
The newer macrolides clarithro- mycin and azithromycin have been
used in pediatric patients for a few years, and it is appropriate
to con- sider their roles in the antimicrobial armamentarium.
Erythromycin is the prototypic macrolide agent and still is the
drug of choice for the treatment of Mycoplasma pneumoniae, Chlamy-
dia pneumoniae, and Legionella pneumophila disease. Clarithro-
mycin has enhanced in vitro activity against group A streptococci
and Staphylococcus aureus compared with erythromycin, and common
pediatric pathogens such as pneu- mococcus, Moraxella catarrhalis,
Mycoplasma pneumoniae, and Chlamydia pneumoniae also are
susceptible. It can be administered twice daily and does not
require refrigeration. Clarithromycin is approved for use in
pediatric patients who have sinusitis, acute otitis media,
pneumonia, group A streptococcal pharyngitis and tonsillitis, and
streptococcal or staphylococcal skin infections. Azithromycin is
less active in vitro than erythromycin against staphylo- cocci and
streptococci, including
pneumococcus. It has higher activity than either erythromycin or
clar- ithromycin for Haemophilus influenzae and similar activity as
clarithromycin for other common pediatric pathogens. However,
azithromycin has unique pharmaco- kinetic properties, with a
terminal phase half-life of approximately 68 hours. This half-life
and the drug’s ability to penetrate into phagocytic and other cells
results in tissue levels persisting for 4 to 7 days after treatment
is stopped. It is given once daily and also does not require
refrigeration. Approved pediatric indications include pneu- monia,
acute otitis media, and pharyngitis/tonsillitis; the latter
indication requires a higher dosing regimen.
In adults, both clarithromycin and azithromycin have many fewer
gastrointestinal side effects than does erythromycin, but this
differ- ence is not as dramatic in children.
IN BRIEF
Michael J. Ackerman Consultation with the Specialist: The Long QT
Syndrome
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